Turner Christi N, Mullins Genevieve N, Hoyer Katrina K
Quantitative and Systems Biology Graduate Program, University of California, Merced, Merced, CA, United States.
Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA, United States.
Front Med (Lausanne). 2022 Oct 13;9:1034764. doi: 10.3389/fmed.2022.1034764. eCollection 2022.
CXCR5CD8 T cells have attracted significant interest within multiple areas of immunology, cancer, and infection. This is in part due to their apparent dual functionality. These cells perform as cytotoxic cells in a variety of infection states including LCMV, HBV, HIV and SIV. However, CXCR5CD8 T cells also associate with B cells in peripheral organs and function to stimulate B cell proliferation, antibody/B cell receptor class-switch, and antibody production. CXCR5CD8 T cells are similar to CXCR5CD4 T follicular helpers in their genetic make-up, B cell interactions, and functionality despite possessing elevated programmed cell death 1 and cytotoxic proteins. Within cancer CXCR5CD8 T cells have risen as potential prognostic markers for overall survival and are functionally cytotoxic within tumor microenvironments. In inflammatory disease and autoimmunity, CXCR5CD8 T cells are implicated in disease progression. During viral infection and cancer, CXCR5 expression on CD8 T cells generally is indicative of progenitor memory stem-like exhausted cells, which are more responsive to immune checkpoint blockade therapy. The use of immune checkpoint inhibitors to overcome immune exhaustion in cancer, and subsequent consequence of immune adverse events, highlights the dual nature of the cellular immune response. This review will detail the functionality of CXCR5CD8 T cells in cancer and autoimmunity with potential repercussions during immune checkpoint blockade therapy discussed.
CXCR5⁺ CD8⁺ T细胞在免疫学、癌症和感染的多个领域引起了广泛关注。部分原因在于它们明显的双重功能。这些细胞在包括淋巴细胞脉络丛脑膜炎病毒（LCMV）、乙肝病毒（HBV）、人类免疫缺陷病毒（HIV）和猴免疫缺陷病毒（SIV）在内的多种感染状态下发挥细胞毒性作用。然而，CXCR5⁺ CD8⁺ T细胞也在外周器官中与B细胞相互作用，并刺激B细胞增殖、抗体/B细胞受体类别转换以及抗体产生。尽管CXCR5⁺ CD8⁺ T细胞程序性细胞死亡蛋白1和细胞毒性蛋白水平升高，但其在基因组成、与B细胞的相互作用及功能方面与CXCR5⁺ CD4⁺ T滤泡辅助细胞相似。在癌症中，CXCR5⁺ CD8⁺ T细胞已成为总体生存的潜在预后标志物，且在肿瘤微环境中具有细胞毒性功能。在炎症性疾病和自身免疫中，CXCR5⁺ CD8⁺ T细胞与疾病进展有关。在病毒感染和癌症期间，CD8⁺ T细胞上CXCR5的表达通常表明祖细胞记忆样耗竭细胞，这些细胞对免疫检查点阻断疗法更敏感。使用免疫检查点抑制剂来克服癌症中的免疫耗竭以及随后免疫不良事件的后果，凸显了细胞免疫反应的双重性质。本综述将详细阐述CXCR5⁺ CD8⁺ T细胞在癌症和自身免疫中的功能，并讨论免疫检查点阻断疗法期间的潜在影响。
